1,499 research outputs found
SERPINB3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by inducing a more tolerogenic immune phenotype
Objective: To explore the effects of SERPINB3 administration in murine lupus models with a focus on lupus-like nephritis. Methods: 40 NZB/W F1 mice were subdivided into 4 groups and intraperitoneally injected with recombinant SERPINB3 (7.5 \u3bcg/0.1 mL or 15 \u3bcg/0.1 mL) or PBS (0.1 mL) before (group 1 and 2) or after (group 3 and 4) the development of proteinuria ( 65100 mg/dl). Two additional mice groups were provided by including 20 MRL/lpr mice which were prophylactically injected with SERPINB3 (10 mice, group 5) or PBS (10 mice, group 6). Time of occurrence and levels of anti-dsDNA and anti-C1q antibodies, proteinuria and serum creatinine, overall- and proteinuria-free survival were assessed in mice followed up to natural death. Histological analysis was performed in kidneys of both lupus models. The Th17:Treg cell ratio was assessed by flow-cytometry in splenocytes of treated and untreated MRL/lpr mice. Statistical analysis was performed using non parametric tests and Kaplan-Meier curves, when indicated. Results: Autoantibody levels and proteinuria were significantly decreased and time of occurrence significantly delayed in SERPINB3-treated mice vs. controls. In agreement with these findings, proteinuria-free and overall survival were significantly improved in SERPINB3-treated groups vs. controls. Histological analysis demonstrated a lower prevalence of severe tubular lesions in kidneys of group 5 vs. group 6. SERPINB3-treated mice showed an overall trend toward a reduced prevalence of severe lesions in both strains. Th17:Treg ratio was significantly decreased in splenocytes of MRL/lpr mice treated with SERPINB3, compared to untreated control mice. Conclusions: SERPINB3 significantly improves disease course and delays the onset of severe glomerulonephritis in lupus-prone mice, possibly inducing a more tolerogenic immune phenotype
Effects of royal jelly on genotoxicity and nephrotoxicity induced by valproic acid in albino mice
AbstractEpilepsy is one of the most common neurological diseases affecting at least 50 million people worldwide. Valproic acid (VPA) is a widely used antiepileptic medication for both generalized and partial seizures of epilepsy. The objective of the study was to investigate the anti-mutagenic and anti-histopathologic effects of royal jelly (RJ) on VPA-induced genotoxicity and nephrotoxicity in male albino mice (Mus musculus). 80 Mice were used for 21 days; they were divided into eight groups, (G1) served as normal control group, G2 received VPA (100 mg/kg) and (G3–G5) received RJ at doses 50, 100 and 200 mg/kg respectively. While (G6–G8) were administrated RJ simultaneously with VPA. In RJ treated mice at doses of 50 and 100 mg/kg, the kidney sections showed normal histological structure with non significant changes in chromosomal aberrations (CA) and mitotic index (MI), while RJ at dose of 200 mg/kg showed mild inflammatory cells infiltration and hyperemic glomeruli but not highly significant changes in CA and MI. The cortex of VPA treated mice revealed congested glomeruli with inflammatory cells infiltration, and marked degeneration of almost structures of the glomeruli including some vacuoles in mesangial cells with dark mesangial substances on the ultrastructure level. Some proximal tubules showed degeneration of microvilli on the apical parts of some cells. Cells of the distal tubules attained obliterated lumen and vacuolated lining epithelium. The results also revealed that valproic acid induced a high frequency of CA in bone marrow cells of mice and MI was significantly decreased indicating bone marrow cytotoxicity. The treatment of mice with RJ at doses 50, 100 and 200 mg/kg for 21 days simultaneously with VPA resulted in abating the histological alterations in renal tissues with significant reduction in chromosomal aberrations, for doses of 50 and 100 mg/kg, and elevation in mitotic index (P < 0.05). RJ at doses 50 and 100 mg/kg appeared more potent in exerting the ameliorative effect
Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs
This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n =11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and
immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related.info:eu-repo/semantics/publishedVersio
Joint and individual analysis of breast cancer histologic images and genomic covariates
A key challenge in modern data analysis is understanding connections between
complex and differing modalities of data. For example, two of the main
approaches to the study of breast cancer are histopathology (analyzing visual
characteristics of tumors) and genetics. While histopathology is the gold
standard for diagnostics and there have been many recent breakthroughs in
genetics, there is little overlap between these two fields. We aim to bridge
this gap by developing methods based on Angle-based Joint and Individual
Variation Explained (AJIVE) to directly explore similarities and differences
between these two modalities. Our approach exploits Convolutional Neural
Networks (CNNs) as a powerful, automatic method for image feature extraction to
address some of the challenges presented by statistical analysis of
histopathology image data. CNNs raise issues of interpretability that we
address by developing novel methods to explore visual modes of variation
captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features.
Our results provide many interpretable connections and contrasts between
histopathology and genetics
Effects Of Catha edulis’ Leaf Extract on Blood Chemistry and Kidney Tissues in Small East African Male Goats from Rift Valley Province of Kenya
Objectives: To determine the serum electrolytes levels in animals treated with Catha edulis leaf extract.Design: Experimental studySetting: Department of Biological Sciences at the Chepkoilel University College, Moi UniversitySubjects: Fourteen (14) reproductively mature and healthy small East African male goats (Capra aegagrus hircus) from Kerio Valley in Rift Valley province of Kenya.Intervention: Plasma electrolytes (Na+, K+, Ca2+ and Cl-), urea, creatine and glucose levels were investigated in eight control and fourteen experimental small East African male goats before and after treatment with Catha edulis leaf extracts. At the end of the study the animals’ were sacrificed and their kidneys extracted for histological examination.Results: mean sodium and calcium levels were lower in treated animals than nontreated animals (138 v/s 143.6 mmol/L and 3.3 v/s 2.2 mmol/L respectively), p<0.001 Plasma glucose levels also declined from 4.0-4.1mmol/L to 3.3-3.5mmol/L following the Catha edulis leaf extract treatment. However serum nitrogenous metabolites levels increased significantly in Catha edulis treated animals (urea; 6.5 v/s 5.2 mmol/L andcreatine; 69.9 v/s 55.4 mmol/L). Histological examination of renal tissue of Catha edulis treated animals revealed degenerative changes and hypercellularity in the glomeruli as well as interstitial inflammatory cell infiltration. Nuclei of proximal convoluted tubule cells also appeared pyknotic while those of the macula densa appeared granular.Conclusion: The present study showed that Catha edulis treatment was associated with electrolyte imbalance which may have been as a result of degenerative changes in the renal system. The findings are a pointer to the fact that Catha edulis use may predispose the users to renal disorders and subsequent electrolyte imbalance
The Role of Toll-Like Receptor 2 in Inflammation and Fibrosis during Progressive Renal Injury
Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2−/− or TLR2+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-β in kidneys of TLR2−/− mice compared with TLR2+/+ animals. Although, the obstructed kidneys of TLR2−/− mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis
Mesenchymal stem cells in renal function recovery after acute kidney injury. Use of a differentiating agent in a rat model.
Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells
Assessment of biosafety and fillet-residues After florfenicol exposures in Trachinotus blochii to ensure safe applications in disease incidences
Trachinotus blochii is a promising mariculture fish species. Scientific data on biosafety
and fillet residues of florfenicol exposure, one recommended amphenicol
antimicrobial for aquaculture use, remains unknown in T. blochii, despite its criticality
for prudent application. Accordingly, the paper evaluated the safety (regarding
mortality, symptoms, weight gain, and histopathology) of dietary florfenicol after
therapeutic (10 mg Kg-1 for ten days) and excessive (three, five, and ten times the
therapeutic dose for 10, 20, and 30 days) exposures. There was no mortality in any
group. The clinical abnormalities were noted only in 10X group from the 25th exposure
day, which disappeared on the fourth day after withdrawal. Reduced growth was
recorded at 5X and 10X groups from 20 and 30 exposure days, respectively.
Histological lesion’s severity was in the liver > kidney > gill > spleen > muscle >
intestine. The lesion severity relied on the quantity and duration of exposures, with
maximum severity in 5X and 10X groups on the 30th day. After recommended
therapeutic exposure, fillet residues were below the maximum residual limit accepted
by the European Union (1000 µg Kg-1) from day three of the withdrawal, showing a
minimum three-day is necessary to reach a safe, acceptable level
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